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Edmond Rogers Dissertation, Elucidating pathological correlations between traumatic brain injury and Alzheimer’s Disease

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<p>Traumatic Brain Injuries (TBI) are a major cause of disability and death in the United States. One of the greatest consequences of the disease is the resulting long-term damage, especially in milder injury cases where the damage is initially subclinical and thus lacking acutely observable manifestations that over time can compound significantly. Among these chronic issues, Alzheimer’s Disease (AD) is one of the most serious. While multiple studies demonstrate an increased likelihood of developing neurodegenerative diseases in response to TBI, the underlying mechanisms remain undefined and no current treatment options are available. Multiple hypotheses have been postulated based on various animal and clinical models, which have contributed a great deal to our current knowledge base and implicated several targets of interest in this pathway (i.g. oxidative stress, inflammation, disruptions in proteostasis). While extremely valuable, these <em>in vivo</em> procedures and analyses are physiologically and ethically complex: there is currently no model capable of separating and visualizing TBI-induced sub-cellular damage in the moments (seconds) immediately following injury, and the subsequent associated long-term changes (AD). In addition, no mechanistic study has been performed to link mechanical-trauma independently with neurodegeneration initiation via protein aggregation. It is clear that additional investigative tools are needed to rectify these intricate issues, and while <em>in vitro </em>methodologies generally offer the type of resolution required, no such model replicates these phenomena. Therefore, we introduce the “TBI-on-a-chip” <em>in vitro </em>concussive model, with a series of concomitant targeted-experiments to address this urgent, currently unmet need. This dissertation work describes the development of our cellular trauma model, featuring a multi-disciplinary approach that provides investigatory opportunities into cellular mechanics, molecular biology, functional alterations (electrophysiology), and morphology, in both primary and secondary injury. Utilizing this model, we directly observe evidence of impact-induced electrical/functional and biochemical consequences, in addition to isolating oxidative stress as a key, contributing component. Taken together, these collective efforts suggest that oxidative stress may be a viable target for both acute and chronic potential therapeutic interventions.</p>

  1. 10.25394/pgs.22592626.v1
Identiferoai:union.ndltd.org:purdue.edu/oai:figshare.com:article/22592626
Date19 April 2023
CreatorsEdmond Rogers (15212116)
Source SetsPurdue University
Detected LanguageEnglish
TypeText, Thesis
RightsCC BY 4.0
Relationhttps://figshare.com/articles/thesis/Edmond_Rogers_Dissertation_Elucidating_pathological_correlations_between_traumatic_brain_injury_and_Alzheimer_s_Disease/22592626

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